In its ideal form, cancer therapy harnesses the innate immunity of the host mammal and specifically humans, suffering from cancerous cell growth, to combat malignancy. Spontaneously arising clones of malignant cells are normally eradicated through mechanisms involving mononuclear cells such as natural killers (NK) and lymphokine activated (LAK) cells. It has been suggested that the functionality of such cells is modulated by locally released inflammatory mediators, such as prostaglandins and leukotrienes, which are products of the eicosanoid biosynthetic pathway. Changes in the amount of locally released eicosanoids thus may alter the activity of NK/LAK cells.
Malignant gliomas (glial cells which have undergone malignant transformation) of the central nervous system are particularly difficult to treat effectively, since they frequently arise at surgically inaccessible sites in the central nervous system and they tend to be resistant to the standard cancer treatments of chemotherapy and radiation. Though malignant gliomas tend to be non-metastatic, they nevertheless cause death by pressure on vital centers as a consequence of their continued growth. Median survival, even in treated patients, is no more than about eighteen months.
Tumors of gliomas have been found to synthesize at least one polypeptide growth factor, basic fibroblast growth factor (bFGF), which stimulates production of eicosanoids, particularly PGE.sub.2. This suggests that growth of gliomas, in vivo, is driven by bFGF and/or PGE.sub.2.
As a start in determining a means for controlling eicosanoids it is initially known that eicosanoids are formed from arachidonic acid (AA) by one of two major pathways. Prostanoids, which tend to inhibit cytotoxic activity of NK and LAK cells, are formed as the result of hydrolysis of AA by the enzyme cyclooxygenase. These prostanoids include prostaglandins of the E and F series, prostacyclin, and thromboxanes. In the other major pathway, leukotrienes are formed by AA acted upon by lipoxygenases, particularly 5-lipoxygenase. Nearly all currently available non-steroidal antiinflammatory drugs operate through inhibition of cyclooxygenase activity.
A limiting step in the eicosanoid biosynthetic pathway is the generation of the intracellular AA. Formation of AA, which results in prostanoid production, occurs from the action of phospholipase A.sub.2 (PLA.sub.2). Recently, several natural activators of PLA.sub.2 have been identified. Venoms, particularly of origin from bees and wasps, have been known to incite local tissue inflammation through generation of eicosanoids. The protein, mellitin, found in bee venom, has been discovered as having the capacity to enhance PLA.sub.2 enzyme activity. Mellitin shows homology with phospholipase activating protein (PLAP) which has been isolated from the joint fluids of patients suffering from rheumatoid arthritis. Synthetic peptides corresponding to shared sequences of mellitin and PLAP have been recently shown to have the capacity to activate PLA.sub.2 both in vitro and in vivo, with the induced release of PGE.sub.2. Growth of gliomas is experimentally shown to be associated with the synthesis and release of PGE.sub.2, PGF.sub.1.alpha., PGF.sub.2.alpha., and leukotriene B.sub.4 (LTB.sub.4).